Evolution evolves: physiology returns to centre stage

Abstract

This issue of The Journal of Physiology is devoted to the integration of evolutionary biology with physiological science. The immediate trigger was a very successful symposium on this theme held during the IUPS Congress in Birmingham in July 2013. The symposium followed an opening plenary lecture based on an article that had recently been published by one of us in the sister journal Experimental Physiology (Noble, 2013) and previously in The Journal of Physiology (Noble, 2011). The title of that article was ambitious, describing physiology as 'rocking the foundations' of biology. Strong language, perhaps? Yes, but that title was merely reflecting a rising tide of recently published articles in major scientific journals, including Nature Reviews Genetics (Müller, 2007), Proceedings of the National Academy of Sciences of the USA (Mattick, 2012), Nature (Ball, 2013), Biological Journal of the Linnean Society (Bateson, 2014) and Science (Rosenberg & Queitsch, 2014). It was also prompted by important books that have appeared recently (Margulis & Sagan, 2003; Jablonka & Lamb, 2014; Noble, 2006; Beurton et al. 2008; Pigliucci & Müller, 2010; Bateson & Gluckman, 2011; Gissis & Jablonka, 2011; Shapiro, 2011). Those books also propose either significant extensions of existing evolutionary theory or the replacement of the Modern Synthesis by a new synthesis. Despite the radical presentation of the Experimental Physiology article, therefore, it contains little that was not already known to those biologists who have been keeping abreast of recent literature. It is becoming increasingly difficult to keep up with this literature because it is widely spread amongst very many scientific journals. A focused issue of a journal, like this one, can therefore be very valuable. We intend that this should be a seminal resource for future research and teaching. Why have these questions become important? One answer is that they change the way in which physiological function is relevant to evolutionary biology. We define function here as the role that a part, a process or a mechanism plays within an encompassing system, a role that contributes to the goal-directed behaviour of that system. This definition covers different notions, such as those presented by Wright (1973), Cummins (1975) and Kitcher (1993). There is a possible confusion in discussing function in the context of evolution because current utility is not necessarily how the trait evolved. Further reading on these issues can be found in the articles by Tinbergen (1963), Bateson & Laland (2013) and the one in this issue by Roux (2014). We are also using a broad definition of physiology as a discipline at the intersection of ecology, behavioural biology, developmental biology and molecular biology. As will be evident in the articles of this focused issue, the new developments encompass all these fields, often in combination. In standard selection theory, usually called the Modern Synthesis (MS) and sometimes called Neo-Darwinism, function is relevant only to postgenomic change in populations through determining which individuals are successful in reproducing. One of the dogmas of the Modern Synthesis is the impossibility of the inheritance of acquired developmental dispositions. Genomic change, which is seen within the MS framework as a synonym to hereditary change, is assumed to be random with respect to function. Function therefore plays a role only in so far as it determines the fitness of the individual organism in its reproductive success after genomic mutations have created the possibility of an advantage. In contrast, the inheritance of some acquired epigenetic characteristics and other forms of non-DNA inheritance enables function to be involved in pregenomic change by influencing hereditary change more directly before selection could play a role. Furthermore, mechanisms of genomic change have been identified that were not envisaged by the founders of the Modern Synthesis, including symbiogenesis and natural genetic engineering. Making a categorical prohibition a central part of a theory can be useful for a time. The Modern Synthesis served an important function in the mid-20th century in stimulating much mathematical work in population genetics, for example. But we have to recognize that by encouraging a dogmatic use of the theory it may also have inhibited many lines of research that have now been found to be important. Theories with categorical prohibitions court their own demise, requiring either fundamental extensions or even complete replacement when contrary experimental evidence emerges. The articles in this issue demonstrate that evidence. The mechanism of random change followed by selection becomes only one of many possible mechanisms of evolutionary change. Moreover, all those mechanisms can interact. We have entered a period of a systems approach to evolution science that contrasts markedly with the parsimonious reductionism of the Modern Synthesis. In this respect, it echoes the move towards a systems approach in many other areas of biology (Melham et al. 2013). The genotype–phenotype relation, which is at the heart of our view of heredity and development, has turned out to be much more subtle than what the Modern Synthesis made room for, and it is increasingly acknowledged that a better understanding of this relation is key to understanding a range of evolutionary phenomena beyond the explanatory reach of the Modern Synthesis. Considering that the disciplinary goals of physiology are 'the study of the functions and activities of living matter (as of organs, tissues, or cells) as such and of the physical and chemical phenomena involved' (Webster's Third New International Dictionary), it is clear that the mechanistic aspects of the genotype–phenotype relation lie within the explanatory domain of physiology. Hence, physiology must of necessity become the backbone of any mature evolutionary theory pretending to merge the proximate and ultimate explanatory domains. The consequence is that we will have to go back to a broader, more inclusive view of heredity, which was captured by William Bateson's original definition of genetics as 'The Physiology of Descent' (Bateson, 1906; see Olby, 2000). A physiological view of heredity enables the integration of the extended evolutionary synthesis view of evolution with the physiological sciences. More specifically, the genotype–phenotype concept that is currently in wide use within evolutionary theory conceals the facts that it is an abstraction of a relation that is the outcome of very complex dynamics that in many cases are intimately connected to the environment (Gjuvsland et al. 2013), and that DNA does not have the privileged place in the chain of causality many attribute to it. As described in more detail by Omholt (2013), if one tries to interpret the function of DNA in systemic terms one finds that DNA allows a system to induce perturbations of its own dynamics as a function of the system's own state (its phenome). In this systems view, the causality flows from the system state through a change in use of DNA that results in a change in the production of RNA and protein, which in turn perturbs the system's dynamics. In those cases where variations in DNA cause changes in the perturbation regimen, it may lead to different system dynamics and thus physiological variation. Thus, the genotype–phenotype relation cannot be understood outside a systems-physiology framework, whatever causes variations in DNA. And any evolutionary theory aiming to explain the manifestation of biological form across time and space needs to be highly articulate about this relation. Physiology in a broad sense, therefore, now moves to centre stage in evolutionary biology as we are finally in a position to step conceptually and technologically out of the narrow frames of the Modern Synthesis and take explanatory responsibility for a much wider set of evolutionary phenomena and patterns across time and space. Some of the articles in this issue address the consequences that this new intellectual spotlight has for the discipline of physiology itself, including possible consequences for health and disease; it is noteworthy that some of the new mechanisms manifest themselves in the inheritance of the chances of acquired disease states. The ways in which a systems approach can be applied to the complex dynamics and evolution of organisms are addressed in this issue by Badyaev (2014), who explores 'whether epigenetic effects facilitate adaptive modulation of complex phenotypes by effectively reducing the dimensionality of their deterministic networks'; Baverstock & Rönkkö (2014), who regard the cell 'as a complex dissipative natural process' that 'minimizes the free energy of their ecosystems', a process where genetic variation is largely irrelevant; Jaeger & Monk (2014) showing 'how dynamical systems theory can provide a unifying conceptual framework for evolution of biological regulatory systems'; Lamm (2014), who 'applies the conceptual toolkit of Evolutionary Developmental Biology (evo–devo) to the evolution of the genome and the role of the genome in organism development'; Levin (2014), who analyses 'the control of anatomy by bioelectricity and the evolutionary implications of its top-down causal efficacy'; and Danchin & Pocheville (2014), who discuss the ways in which 'non-genetic inheritance shatters the frontier between physiology and evolution'. The molecular mechanisms by which non-standard inheritance can occur are diverse. Natural genetic engineering refers to reorganization of genomes. The mechanisms discovered since McClintock (1950, 1984) first demonstrated mobile genetic elements in plants are many. As Beurton et al. (2008) write, 'it seems that a cell's enzymes are capable of actively manipulating DNA to do this or that. A genome consists largely of semi-stable genetic elements that may be rearranged or even moved around in the genome thus modifying the information content of DNA.' In this issue, Shapiro (2014) shows that 'the genome is best modelled as a read–write (RW) data storage system rather than a read-only memory (ROM)'. Symbiogenesis has been involved in the most dramatic examples of genome re-organization, i.e. the acquisition of DNA from other organisms through lateral gene transfer. As is now well known, this is thought to explain the origin of mitochondria, chloroplasts and other organelles. Lateral gene transfer is now recognized to be much more extensive and widespread than it was previously assumed to be; occurring in most orders and often among them. Recent examples include mechanisms of transfer from prokaryotes to eukaryotes generally (Redrejo-Rodríguez et al. 2012) and transfer from bacteria to insects (Acuña et al. 2012). Epigenetic mechanisms that lead to persistent developmentally induced changes in gene activity include diverse processes and factors. One type of system, the chromatin marking system, includes methylation of cytosines and histone modifications, which interact with each other and with other epigenetic control factors (such as small RNAs). Chromatin marks were originally thought to be wiped clean during transmission between generations. It is now clear that this is not always true. Moreover, recent work has shown 'heritable epigenetic changes [that] persisted for multiple generations and were fully reversed after consecutive crosses through the alternative germ-lineage' (Nelson et al. 2012). For example, induced epigenetic (methylation) changes affecting a wide range of characteristics were transmitted for three generations following ancestral exposure to fungicides (e.g. Anway et al. 2006), and conditioned fear to an odorant was transmitted for two generations in mice (Dias & Ressler, 2014). Transmission of epigenetic variations through the germ line is, however, not necessary for inheritance between generations. Chromatin marks can be transmitted across generations by epigenetically marking the genome in the newborn, leading, through their physiological and behavioural effects, to the reconstruction of developmental conditions in the offspring (Weaver, 2009). Such genomic marking may also underlie inherited maternal (Gluckman et al. 2007) and nutritional effects (Kaati et al. 2007). Another non-standard inheritance system, the RNAi-mediated inheritance system, which interacts with the chromatin marking mechanisms, underlies the transmission of many important characteristics in both plants and animals. An example of RNA-transmitted resistance to viruses has been shown to be transmitted stably for 100 generations in nematodes (Rechavi et al. 2011). In this issue, Stern et al. (2014) demonstrate that 'exposure to [antibiotic] stress reduces the maternal levels of Polycomb in the offspring embryos and [that] this reduction contributes to the inheritance of induced expression'. Also in this issue, Bateson et al. (2014) discuss a form of developmental plasticity, the predictive adaptive response (PAR), 'in which cues received in early life influence the development of a phenotype that is normally adapted to the environmental conditions of later life'. Sela et al. (2014) suggest 'that non-coding RNAs synchronize the different transgenerational epigenetic effects by interacting with and therefore surveying both the transcriptome and the genome'. The physiological adjustment of organisms to changes in conditions within and between generations involves corresponding epigenetic changes. Selection for the stabilization of the physiological adjustments can lead both to the selection of epigenetic changes that are inherited between generations and/or to the selection of genetic changes that further stabilize, expand or otherwise improve the physiological adjustments. This process, genetic assimilation, was first demonstrated by Waddington (1957), who also introduced the term 'epigenetics', though not with its current usage. A more inclusive term, 'genetic accommodation', was suggested by Mary-Jane West-Eberhard (2003). This process can lead to the stabilization and canalization of previous developmentally induced changes, to an increase in plasticity and to the buffering of potentially deleterious side-effects. In all cases, the processes are usually initiated by developmental changes that induce new patterns of gene activity in alleles that already exist in the population (but not in that combination in any individual) and expose the new allelic combination to natural selection. No new mutations are required in this process, although a new mutation can contribute to it. Given that it is gene combinations and developmental networks that are the targets of selection, genetic accommodation is yet another process showing the advantages of focusing on networks of interactions rather than on individual 'genes' (we return to the definition of 'gene' later). Thinking through the process of genetic accommodation requires consideration of the interactions between different developmental mechanisms at different levels of biological organization. Following genetic accommodation, the inheritance becomes standard DNA inheritance; therefore, it would be difficult to determine from genomic sequencing whether this process had occurred. However, comparisons of chromatin marking and small RNA profiles in populations that are at the initial stages of evolutionary divergence can uncover the epigenetic correlates of the physiological adjustments that drive genetic assimilation and can point to epigenetic factors that are inherited and contribute to the stabilization of the new adjustments. Further valuable insights on these questions can be found in the article in this issue by Bateson et al. 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